Details for: CYP2C19

Gene ID: 1557

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: CYP2C19

Ensembl ID: ENSG00000165841

Description: cytochrome P450 family 2 subfamily C member 19

Selected Context(s):  Overall

Cell Significance Landscape

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Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • enterocyte of epithelium of small intestine CL1000334
    CSI 0.58
    rCSI 8.91%
    PRS 100

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [CYP2C19](/details-gene/1557), or Cytochrome P450 family 2 subfamily C member 19, is a protein-coding gene located on chromosome 10q23.33. It encodes a critical monooxygenase enzyme that is a member of the cytochrome P450 superfamily. This enzyme is primarily localized to the `[endoplasmic reticulum membrane](/details-go/GO:0005789)` and plays a central role in the metabolism of a wide array of endogenous and exogenous compounds. Its function is particularly significant in the metabolic processing of steroids, fatty acids, and numerous xenobiotics, including a large number of clinically prescribed drugs. Expression data indicates a highly specific role for [CYP2C19](/details-gene/1557) within the gastrointestinal tract, with significant expression observed in the `[enterocyte of epithelium of small intestine](/details-cell/CL1000334)`. Polymorphisms in this gene are well-documented and are associated with variable drug metabolism phenotypes, which has major implications for clinical pharmacology ([124020](https://omim.org/entry/124020)). ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [CYP2C19](/details-gene/1557) suggests a highly specialized function rather than a ubiquitous role. The available data highlight its most significant expression in the `[enterocyte of epithelium of small intestine](/details-cell/CL1000334)` (CSI: 0.58). This prominent expression in intestinal epithelial cells is consistent with its established function in the first-pass metabolism of orally administered drugs and other xenobiotics absorbed from the gut. As enterocytes form the primary barrier and metabolic interface between the external environment and the body's internal circulation, the high activity of [CYP2C19](/details-gene/1557) in these cells underscores its importance in detoxification and the regulation of compound bioavailability. The lack of broader expression data in other tissues suggests that its primary biological impact may be concentrated within this specific anatomical niche. ## Pathways and Molecular Function [CYP2C19](/details-gene/1557) functions as a monooxygenase, possessing `[heme binding](/details-go/GO:0020037)`, `[iron ion binding](/details-go/GO:0005506)`, and `[oxidoreductase activity](/details-go/GO:0016491)`. Its enzymatic activity is integral to several key metabolic pathways. A major role of this enzyme is in the `[Xenobiotic metabolic process](/details-go/GO:0006805)`, as detailed in Reactome pathways such as `[Phase i - functionalization of compounds](/details-pathway/R-HSA-211945)`, `[Xenobiotics](/details-pathway/R-HSA-211981)`, and `[Drug adme](/details-pathway/R-HSA-9748784)`. This is supported by numerous studies demonstrating its role in metabolizing drugs like S-mephenytoin ([Link](https://doi.org/10.1006/abbi.1993.1506)) and albendazole ([Link](https://doi.org/10.1128/aac.00843-13)). In addition to xenobiotics, [CYP2C19](/details-gene/1557) is involved in the metabolism of endogenous substrates. It contributes to the `[Steroid metabolic process](/details-go/GO:0008202)` and `[Long-chain fatty acid metabolic process](/details-go/GO:0001676)`. Its involvement in lipid metabolism is further specified by its `[Arachidonate epoxygenase activity](/details-go/GO:0008392)` and its role in pathways like `[Arachidonate metabolism](/details-pathway/R-HSA-2142753)` and `[Metabolism of lipids](/details-pathway/R-HSA-556833)`. These functions suggest a role in producing signaling molecules derived from fatty acids, which can influence physiological processes such as inflammation and vascular tone. ## Research Directions Given the critical role of [CYP2C19](/details-gene/1557) in drug metabolism and its specific expression in the gut, future research could explore its interplay with environmental factors and its contribution to localized tissue homeostasis. ### Proposed Hypotheses: 1. Genetic variants of [CYP2C19](/details-gene/1557) that alter enzymatic activity in `[enterocytes of epithelium of small intestine](/details-cell/CL1000334)` directly influence the composition of the gut microbiome by modifying the metabolism of dietary phytochemicals and microbial products, thereby impacting host-microbe symbiosis. 2. The `[arachidonate epoxygenase activity](/details-go/GO:0008392)` of [CYP2C19](/details-gene/1557) within the intestinal epithelium is a significant local regulator of inflammation. Reduced activity due to genetic polymorphisms or inhibition may lead to an imbalance of pro- and anti-inflammatory eicosanoids, predisposing individuals to inflammatory bowel disease. ### Key Experiment: To test the second hypothesis regarding the role of [CYP2C19](/details-gene/1557) in intestinal inflammation, a multi-faceted approach using patient-derived intestinal organoids could be employed. Organoids could be established from biopsies of healthy individuals and IBD patients who have been genotyped for common functional variants of [CYP2C19](/details-gene/1557) (e.g., *2, *3, *17 alleles). These organoids would then be exposed to inflammatory stimuli like TNF-α. The functional consequence of [CYP2C19](/details-gene/1557) activity would be assessed by performing lipidomic analysis using mass spectrometry to quantify the production of specific epoxy- and dihydroxyeicosatrienoic acids (EETs and DHETs). Concurrently, the inflammatory response could be measured by quantifying the secretion of cytokines like IL-6 and IL-8 via ELISA. This experiment would directly link [CYP2C19](/details-gene/1557) genotype and metabolic function to the inflammatory capacity of the intestinal epithelium. ### Therapeutic Potential: The therapeutic relevance of [CYP2C19](/details-gene/1557) is primarily centered on pharmacogenomics rather than direct modulation of the enzyme as a therapeutic target. Its well-characterized polymorphisms, which create poor, intermediate, extensive, and ultrarapid metabolizer phenotypes, have profound effects on the efficacy and toxicity of numerous drugs, including the antiplatelet agent clopidogrel, proton pump inhibitors, and antidepressants. Therefore, the main clinical application is the use of genetic testing for [CYP2C19](/details-gene/1557) alleles to guide personalized drug selection and dosing. This predictive approach aims to optimize therapeutic outcomes and minimize adverse drug events, making [CYP2C19](/details-gene/1557) a cornerstone of personalized medicine ([Link](https://doi.org/10.1002/cpt.690)).

Genular Protein ID: 3604756082

Symbol: CP2CJ_HUMAN

Name: Cytochrome P450 2C19

UniProtKB Accession Codes:

P33261 P33259 Q8WZB1 Q8WZB2 Q9UCD4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 115 ChEMBL 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 337 DrugCentral 1 EC 5 EMBL 16 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 25 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 2 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PIR 3 PRINTS 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 5 RefSeq 1 Rhea 60 SABIO-RK 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissLipids 1 TreeFam 1 UCSC 1 UniPathway 2 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 2009263

Title: Cloning and expression of complementary DNAs for multiple members of the human cytochrome P450IIC subfamily.

PubMed ID: 2009263

DOI: 10.1021/bi00227a012

PubMed ID: 8095407

Title:

PubMed ID: 8095407

DOI: 10.1021/bi00056a025

PubMed ID: 15164054

Title: The DNA sequence and comparative analysis of human chromosome 10.

PubMed ID: 15164054

DOI: 10.1038/nature02462

PubMed ID: 8215410

Title: Isolation and characterization of human liver cytochrome P450 2C19: correlation between 2C19 and S-mephenytoin 4'-hydroxylation.

PubMed ID: 8215410

DOI: 10.1006/abbi.1993.1506

PubMed ID: 11950794

Title: Metabolism of (+)- and (-)-limonenes to respective carveols and perillyl alcohols by CYP2C9 and CYP2C19 in human liver microsomes.

PubMed ID: 11950794

DOI: 10.1124/dmd.30.5.602

PubMed ID: 18577768

Title: Cytochromes P450 from family 4 are the main omega hydroxylating enzymes in humans: CYP4F3B is the prominent player in PUFA metabolism.

PubMed ID: 18577768

DOI: 10.1194/jlr.m800199-jlr200

PubMed ID: 19965576

Title: Stereoselective epoxidation of the last double bond of polyunsaturated fatty acids by human cytochromes P450.

PubMed ID: 19965576

DOI: 10.1194/jlr.m003061

PubMed ID: 20972997

Title: Analysis of epoxyeicosatrienoic acids by chiral liquid chromatography/electron capture atmospheric pressure chemical ionization mass spectrometry using [13C]-analog internal standards.

PubMed ID: 20972997

DOI: 10.1002/rcm.4760

PubMed ID: 23959307

Title: CYP2J2 and CYP2C19 are the major enzymes responsible for metabolism of albendazole and fenbendazole in human liver microsomes and recombinant P450 assay systems.

PubMed ID: 23959307

DOI: 10.1128/aac.00843-13

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 28378927

Title: Worldwide Distribution of Cytochrome P450 Alleles: A Meta-analysis of Population-scale Sequencing Projects.

PubMed ID: 28378927

DOI: 10.1002/cpt.690

PubMed ID: 23118231

Title: Structural characterization of human cytochrome P450 2C19: active site differences between P450s 2C8, 2C9, and 2C19.

PubMed ID: 23118231

DOI: 10.1074/jbc.m112.424895

PubMed ID: 8195181

Title: The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans.

PubMed ID: 8195181

DOI: 10.1016/s0021-9258(17)40694-6

PubMed ID: 7969038

Title: Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese.

PubMed ID: 7969038

PubMed ID: 9103550

Title: Differences in the incidence of the CYP2C19 polymorphism affecting the S-mephenytoin phenotype in Chinese Han and Bai populations and identification of a new rare CYP2C19 mutant allele.

PubMed ID: 9103550

PubMed ID: 9732415

Title: Identification of new human CYP2C19 alleles (CYP2C19*6 and CYP2C19*2B) in a Caucasian poor metabolizer of mephenytoin.

PubMed ID: 9732415

PubMed ID: 10022751

Title: An additional defective allele, CYP2C19*5, contributes to the S-mephenytoin poor metabolizer phenotype in Caucasians.

PubMed ID: 10022751

DOI: 10.1097/00008571-199804000-00006

PubMed ID: 10411572

Title: A novel transversion in the intron 5 donor splice junction of CYP2C19 and a sequence polymorphism in exon 3 contribute to the poor metabolizer phenotype for the anticonvulsant drug S-mephenytoin.

PubMed ID: 10411572

PubMed ID: 12464799

Title: Identification and functional characterization of new potentially defective alleles of human CYP2C19.

PubMed ID: 12464799

DOI: 10.1097/00008571-200212000-00004

PubMed ID: 15499191

Title: A novel single nucleotide polymorphism (SNP) of the CYP2C19 gene in a Japanese subject with lowered capacity of mephobarbital 4'-hydroxylation.

PubMed ID: 15499191

DOI: 10.2133/dmpk.19.236

PubMed ID: 15469410

Title: Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population.

PubMed ID: 15469410

DOI: 10.1517/14622416.5.7.895

PubMed ID: 16141610

Title: Genetic variations and haplotypes of CYP2C19 in a Japanese population.

PubMed ID: 16141610

DOI: 10.2133/dmpk.20.300

Sequence Information:

  • Length: 490
  • Mass: 55945
  • Checksum: B451BFFE9A009465
  • Sequence:
    • MDPFVVLVLC LSCLLLLSIW RQSSGRGKLP PGPTPLPVIG NILQIDIKDV SKSLTNLSKI 
YGPVFTLYFG LERMVVLHGY EVVKEALIDL GEEFSGRGHF PLAERANRGF GIVFSNGKRW 
KEIRRFSLMT LRNFGMGKRS IEDRVQEEAR CLVEELRKTK ASPCDPTFIL GCAPCNVICS 
IIFQKRFDYK DQQFLNLMEK LNENIRIVST PWIQICNNFP TIIDYFPGTH NKLLKNLAFM 
ESDILEKVKE HQESMDINNP RDFIDCFLIK MEKEKQNQQS EFTIENLVIT AADLLGAGTE 
TTSTTLRYAL LLLLKHPEVT AKVQEEIERV IGRNRSPCMQ DRGHMPYTDA VVHEVQRYID 
LIPTSLPHAV TCDVKFRNYL IPKGTTILTS LTSVLHDNKE FPNPEMFDPR HFLDEGGNFK 
KSNYFMPFSA GKRICVGEGL ARMELFLFLT FILQNFNLKS LIDPKDLDTT PVVNGFASVP 
PFYQLCFIPV